CHMP4B

charged multivesicular body protein 4B, the group of Charged multivesicular body proteins|ESCRT-III

Basic information

Region (hg38): 20:33811347-33854366

Previous symbols: [ "C20orf178" ]

Links

ENSG00000101421 ∙ NCBI:128866 ∙ OMIM:610897 ∙ HGNC:16171 ∙ Uniprot:Q9H444 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 31 multiple types (Strong), mode of inheritance: AD
• early-onset posterior polar cataract (Supportive), mode of inheritance: AD
• early-onset posterior subcapsular cataract (Supportive), mode of inheritance: AD
• cataract 31 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 31, multiple types	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	10682967; 10909854; 17701905

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHMP4B gene.

• not provided (14 variants)
• Cataract 31 multiple types (8 variants)
• Inborn genetic diseases (3 variants)
• not specified (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHMP4B gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2	3	5
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				3	8	11
Total	0	0	8	5	11

Variants in CHMP4B

This is a list of pathogenic ClinVar variants found in the CHMP4B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-33811394-C-G			Benign (Jul 21, 2018)
20-33811506-G-A		not specified	Uncertain significance (Apr 05, 2023)
20-33811884-C-G			Benign (Jul 31, 2018)
20-33848172-C-T			Benign (Jul 21, 2018)
20-33848462-C-T		Cataract 31 multiple types • CHMP4B-related disorder	Benign/Likely benign (Oct 22, 2021)
20-33848476-A-G		Cataract 31 multiple types	Likely pathogenic (Apr 11, 2023)
20-33848495-G-T			Uncertain significance (May 16, 2023)
20-33848497-G-T			Uncertain significance (Feb 03, 2020)
20-33848516-G-A		Cataract 31 multiple types	Likely benign (Mar 06, 2020)
20-33848546-G-A		Cataract 31 multiple types	Benign (Jul 19, 2022)
20-33848586-G-A		Cataract 31 multiple types	Uncertain significance (Feb 08, 2023)
20-33848659-G-A		Cataract 31 multiple types	Likely benign (May 07, 2021)
20-33850969-A-T		Cataract 31 multiple types	Pathogenic (Sep 01, 2007)
20-33851022-A-G		not specified	Uncertain significance (Sep 16, 2021)
20-33851033-G-A		Cataract 31 multiple types	Benign (Jun 29, 2022)
20-33851041-T-C		not specified	Uncertain significance (Feb 13, 2023)
20-33851043-G-A			Uncertain significance (May 20, 2021)
20-33851063-C-T		not specified	Benign (-)
20-33851064-G-A		Cataract 31 multiple types	Pathogenic (Sep 01, 2007)
20-33851064-G-C		Cataract 31 multiple types	Uncertain significance (Mar 21, 2021)
20-33851938-G-T			Likely benign (Oct 13, 2020)
20-33852101-G-T		CHMP4B-related disorder	Uncertain significance (Dec 21, 2023)
20-33852151-C-T		Cataract 31 multiple types	Benign/Likely benign (Oct 03, 2023)
20-33852179-T-G		Cataract 31 multiple types	Uncertain significance (May 02, 2019)
20-33852212-T-C		CHMP4B-related disorder	Likely benign (Jan 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHMP4B	protein_coding	protein_coding	ENST00000217402	5	43063

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.958	0.0422	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.38	53	129	0.411	0.00000734	1473
Missense in Polyphen		12	45.522	0.26361		517
Synonymous	-0.0583	55	54.5	1.01	0.00000361	408
Loss of Function	2.92	0	9.90	0.00	4.30e-7	137

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released (PubMed:12860994, PubMed:18209100). The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:21310966). Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase (PubMed:26040712). Plays a role in the endosomal sorting pathway. ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. When overexpressed, membrane-assembled circular arrays of CHMP4B filaments can promote or stabilize negative curvature and outward budding. CHMP4A/B/C are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). {ECO:0000269|PubMed:12860994, ECO:0000269|PubMed:18209100, ECO:0000269|PubMed:21310966, ECO:0000269|PubMed:22660413, ECO:0000269|PubMed:26040712}.
• Disease: DISEASE: Cataract 31, multiple types (CTRCT31) [MIM:605387]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT31 includes posterior polar, progressive posterior subcapsular, nuclear, and anterior subcapsular cataracts. {ECO:0000269|PubMed:17701905}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Endocytosis - Homo sapiens (human);Necroptosis - Homo sapiens (human);Disease;Vesicle-mediated transport;Membrane Trafficking;Budding and maturation of HIV virion;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;Endosomal Sorting Complex Required For Transport (ESCRT);Infectious disease (Consensus)

Recessive Scores

• pRec: 0.109

Intolerance Scores

• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.643
• hipred: Y
• hipred_score: 0.786
• ghis: 0.571

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.958

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Chmp4b
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: mitotic cytokinesis;posttranslational protein targeting to endoplasmic reticulum membrane;autophagy;nucleus organization;vacuolar transport;mitotic metaphase plate congression;exit from mitosis;regulation of centrosome duplication;endosomal transport;macroautophagy;viral life cycle;nuclear envelope reassembly;multivesicular body assembly;maintenance of lens transparency;viral budding via host ESCRT complex;viral budding;regulation of viral process;protein homooligomerization;negative regulation of cell death;midbody abscission;membrane fission;ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway;negative regulation of neuron death;regulation of mitotic spindle assembly;positive regulation of viral release from host cell;negative regulation of autophagosome assembly
• Cellular component: ESCRT III complex;nucleus;nuclear envelope;cytoplasm;endosome;cytosol;cytoplasmic side of plasma membrane;membrane coat;midbody;late endosome membrane;vesicle;extracellular exosome
• Molecular function: protein binding;identical protein binding;protein homodimerization activity;cadherin binding